Abstract
Background
Dense deposit disease (DDD) is a rare glomerular disease caused by an uncontrolled activation of the alternative complement pathway leading to end-stage renal disease in 50 % of patients. As such, DDD has been classified within the spectrum of complement component 3 (C3) glomerulopathies due to its pathogenesis from alternative pathway dysregulation. Conventional immunosuppressive therapies have no proven effectiveness. Eculizumab, a terminal complement inhibitor, has been reported to mitigate disease in some cases.
Case-diagnosis/treatment
We report on the efficacy of eculizumab in a pediatric patient who failed to respond to cyclophosphamide, corticosteroids, and plasma exchange. Complement biomarker profiling was remarkable for low serum C3, low properdin, and elevated soluble C5b-9. Consistent with these findings, the alternative pathway functional assay was abnormally low, indicative of alternative pathway activity, although neither C3-nephritic factors nor Factor H autoantibodies were detected. Eculizumab therapy was associated with significant improvement in proteinuria and renal function allowing discontinuation of hemodialysis (HD). Repeat C3 and soluble C5b-9 levels normalized, showing that terminal complement pathway activity was successfully blocked while the patient was receiving eculizumab therapy. Repeat testing for alternative pathway activation allowed for a successful decrease in eculizumab dosing.
Conclusions
The case reported here demonstrates the successful recovery of renal function in a pediatric patient on HD following the use of eculizumab.
This is a preview of subscription content, log in via an institution to check access.
References
Smith RJ, Alexander J, Barlow PN, Botto M, Cassavant TL, Cook HT, de Cordoba SR, Hageman GS, Jokiranta TS, Kimberling WJ, Lambris JD, Lanning LD, Levidiotis V, Licht C, Lutz HU, Meri S, Pickering MC, Quigg RJ, Rops AL, Salant DJ, Sethi S, Thurman JM, Tully HF, Tully SP, van der Vlag J, Walker PD, Wurzner R, Zipfel PF (2007) New approaches to the treatment of dense deposit disease. J Am Soc Nephrol 18:2447–2456
McCaughan JA, O’Rourke DM, Courtney AE (2012) Recurrent dense deposit disease after renal transplantation: an emerging role for complementary therapies. Am J Transplant 12:1046–1051
Servais A, Noel LH, Roumenina LT, Le Quintrec M, Ngo S, Dragon-Durey MA, Macher MA, Zuber J, Karras A, Provot F, Moulin B, Grunfeld JP, Niaudet P, Lesavre P, Fremeaux-Bacchi V (2012) Acquired and genetic complement abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies. Kidney Int 82:454–464
De Vriese AS, Sethi S, Van Praet J, Nath KA, Fervenza FC (2015) Kidney disease caused by dysregulation of the complement alternative pathway: an etiologic approach. J Am Soc Nephrol 26:2917–2929
Bomback AS, Smith RJ, Barile GR, Zhang Y, Heher EC, Herlitz L, Stokes MB, Markowitz GS, D’Agati VD, Canetta PA, Radhakrishnan J, Appel GB (2012) Eculizumab for dense deposit disease and C3 glomerulonephritis. Clin J Am Soc Nephrol 7:748–756
Daina E, Noris M, Remuzzi G (2012) Eculizumab in a patient with dense-deposit disease. N Engl J Med 366:1161–1163
Vivarelli M, Pasini A, Emma F (2012) Eculizumab for the treatment of dense-deposit disease. N Engl J Med 366:1163–1165
Ozkaya O, Nalcacioglu H, Tekcan D, Genc G, Meydan BC, Ozdemir BH, Baysal MK, Keceligil HT (2014) Eculizumab therapy in a patient with dense-deposit disease associated with partial lipodystropy. Pediatr Nephrol 29:1283–1287
Sanchez-Moreno A, De la Cerda F, Cabrera R, Fijo J, Lopez-Trascasa M, Bedoya R, Rodriguez de Cordoba S, Ybot-Gonzalez P (2014) Eculizumab in dense-deposit disease after renal transplantation. Pediatr Nephrol 29:2055–2059
Le Quintrec M, Lionet A, Kandel C, Bourdon F, Gnemmi V, Colombat M, Goujon JM, Fremeaux-Bacchi V, Fakhouri F (2015) Eculizumab for treatment of rapidly progressive C3 glomerulopathy. Am J Kidney Dis 65:484–489
Berthe-Aucejo A, Sacquepee M, Fila M, Peuchmaur M, Perrier-Cornet E, Fremeaux-Bacchi V, Deschenes G (2014) Blockade of alternative complement pathway in dense deposit disease. Case Rep Nephrol 2014:201568
Oosterveld MJ, Garrelfs MR, Hoppe B, Florquin S, Roelofs JJ, van den Heuvel LP, Amann K, Davin JC, Bouts AH, Schriemer PJ, Groothoff JW (2015) Eculizumab in pediatric dense deposit disease. Clin J Am Soc Nephrol 10:1773–1782
Rousset-Rouviere C, Cailliez M, Garaix F, Bruno D, Laurent D, Tsimaratos M (2014) Rituximab fails where eculizumab restores renal function in C3nef-related DDD. Pediatr Nephrol 29:1107–1111
Sethi S, Gamez JD, Vrana JA, Theis JD, Bergen HR 3rd, Zipfel PF, Dogan A, Smith RJ (2009) Glomeruli of Dense Deposit Disease contain components of the alternative and terminal complement pathway. Kidney Int 75:952–960
Inman M, Prater G, Fatima H, Wallace E (2015) Eculizumab-induced reversal of dialysis-dependent kidney failure from C3 glomerulonephritis. Clin Kidney J 8:445–448
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
None.
Conflict of interest
The authors declare that they have no conflict of interest.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Supplemental Table 1
(DOCX 15 kb)
Supplemental Table 2
(DOCX 17.5 kb)
Supplemental Figure 1
Response to eculizumab therapy in a patient with dense deposit disease. IV CTX Intravenous cyclophosphamide, PO CTX oral cyclophosphamide, MP methylprednisolone, PLEX plasma exchange. (GIF 46 kb)
Rights and permissions
About this article
Cite this article
Tran, C.L., Sethi, S., Murray, D. et al. Discontinuation of dialysis with eculizumab therapy in a pediatric patient with dense deposit disease. Pediatr Nephrol 31, 683–687 (2016). https://doi.org/10.1007/s00467-015-3306-0
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-015-3306-0